Every year, 400,000 Americans die of lung disease. Of further concern, the death rate due to lung disease is increasing, while the death rates for the other major disease categories are decreasing (heart disease, cancer and stroke). For several lung diseases, including cystic fibrosis, emphysema/COPD, and idiopathic pulmonary fibrosis, lung transplantation remains the only definitive treatment. However, patient survival after lung transplant is only 50% at 5 years and 24% at 10 years [Mondrinos et al., 2008, Tissue Eng 14:361-8]. There is therefore great demand for the development of engineered lung tissue that could be used for transplantation. One advantage of engineered lung tissue is that the tissue can be grown using a patient's own cells, thereby avoiding the need for strong immunosuppression, as is required with current lung transplantation. Immunosuppression is necessary to prevent rejection of the transplanted organ, but can lead to a wide range of problems, including infection, malignancy, kidney impairment, cardiovascular problems, and neurologic disorders [Pietra et al., 2000, J Clin Invest 106:1003-10; Christie et al., 2009, J Heart Lung Transplant 28:1031-49].
Tissue engineering is a growing field that seeks to combine cellular, molecular, technological and medical advances to create replacement tissues suitable for implantation. Promising work has been done on a variety of tissues, including blood vessels, urinary bladder, heart valves, and cardiac tissue [Nichols et al., 2008, Proc Am Thor Soc 5:723-30; Satchell et al., 2004, J Am Soc Nephrol 15:566-74; Atala et al., 2006, Lancet 367:1241-6; Orfanos et al., 2004, Intensive Care Med 30:1702-14]. However, lung is a difficult tissue to engineer in the laboratory. Lung requires a complex matrix that can withstand the mechanical pressures of breathing, that can support the growth of endothelial, epithelial and mesenchymal cells, and that provides a means for gas exchange between two very different yet intimately juxtaposed compartments.
Besides potential patient use in clinical settings, engineered lung tissue can be used in the laboratory to study a wide variety of important aspects of pulmonary biology and physiology. There are very few in vitro 3-dimensional lung culture models [Vandenbroucke et al., 2008, Ann N Y Acad Sci 1123:134-45]. Furthermore, pulmonary endothelial and epithelial cells are more difficult to culture in the laboratory than many other cell types [Malda et al., 2004, Biomaterials 25:5773-80; Reichenspurner, 2005, J Heart Lung Transplant 24:119-30], and there has been relatively slow progress in the field of pulmonary progenitor and stem cell biology [Blaisdell et al., 2009, Stem Cells 27:2263-70; Muratore et al., 2008, J Surg Res 155(2):225-30]. Thus, there is a need in the art for the development of an in vitro lung tissue that replicates key features of the native pulmonary environment. The present invention satisfies this need in the art.